Systemic Exposure Dose (SED): Definition, Calculation and Cosmetic Safety Assessment

Systemic Exposure Dose (SED): Definition, Calculation and Cosmetic Safety Assessment

What Is Systemic Exposure Dose?

Systemic Exposure Dose (SED) is the estimated amount of a cosmetic ingredient that becomes available to the systemic circulation following exposure to a cosmetic product.

SED is expressed in mg/kg body weight/day and is used in the safety assessment of cosmetic ingredients to estimate the level of systemic exposure resulting from their intended use.

Unlike the amount of an ingredient initially applied to the skin, SED takes into consideration factors such as the amount of product used, concentration of the ingredient, frequency of use and the proportion of the ingredient that is absorbed.

How Is SED Calculated?

The calculation of SED depends on the exposure scenario and the available absorption data.

A simplified approach can be expressed as:

SED = E × C × F × DA / BW

Where:

  • E = amount of cosmetic product applied per day
  • C = concentration of the ingredient in the product
  • F = frequency or exposure factor
  • DA = dermal absorption fraction
  • BW = body weight

The specific calculation can vary depending on the exposure route and the methodology used in the safety assessment.

Dermal Absorption and SED

For topical cosmetic products, dermal absorption is an important factor in determining systemic exposure.

Not all of the ingredient applied to the skin necessarily reaches the systemic circulation. The proportion that becomes systemically available depends on the physicochemical characteristics of the ingredient, the formulation, the application site and other exposure-related factors.

When reliable experimental absorption data are available, they can be used in the SED calculation. Where appropriate data are not available, conservative assumptions may be applied as part of the safety assessment.

SED in Cosmetic Safety Assessment

SED is particularly important when evaluating ingredients for which systemic toxicity is a potential concern.

The estimated systemic exposure can be compared with a No Observed Adverse Effect Level (NOAEL) derived from relevant toxicological studies.

This comparison is used to calculate the Margin of Safety (MoS).

A simplified expression is:

MoS = NOAEL / SED

A sufficiently large margin of safety provides support for the conclusion that the expected cosmetic exposure is adequately below the level associated with adverse effects in the relevant toxicological data.

Factors That Influence SED

Several factors can significantly affect the estimated systemic exposure:

Concentration of the Ingredient

A higher concentration of an ingredient in the finished cosmetic product generally results in a higher potential exposure.

Amount of Product Used

The quantity of cosmetic product applied during each use directly influences exposure.

Frequency of Application

Products used several times per day or across large areas of the body can result in greater cumulative exposure.

Dermal Absorption

The percentage of the ingredient that penetrates the skin and becomes systemically available is a key parameter in SED calculation.

Body Weight

SED is normalised to body weight, allowing exposure to be expressed in a standardised form.

Why Is SED Important?

SED provides a quantitative link between cosmetic product use and toxicological safety data.

It allows the safety assessor to move beyond simply considering the concentration of an ingredient in a formulation and instead estimate the actual systemic exposure that may result from normal or reasonably foreseeable use.

For this reason, SED is an important component of professional cosmetic safety assessment and the overall evaluation of cosmetic ingredient safety.

Systemic Exposure Dose (SED) — FAQ

Key questions about SED, its calculation and interpretation in cosmetic safety assessment.

Systemic Exposure Dose (SED) is an estimate of the amount of a cosmetic ingredient that becomes systemically available after exposure. It is commonly expressed as mg/kg body weight/day.
SED tells you the estimated level of systemic exposure under a defined use scenario. By itself, it is not a safety limit and does not determine whether an ingredient is safe or unsafe.
Important factors include the amount of product used, ingredient concentration, application frequency, dermal absorption and body weight. Changing any of these assumptions can change the calculated SED.
A simplified topical-exposure calculation can be represented as follows:
SED = (Product Use × Ingredient Concentration × Frequency × Dermal Absorption) ÷ Body Weight
A lower estimated exposure generally means lower systemic exposure under the same assumptions, but safety cannot be concluded from SED alone. The exposure must be compared with relevant toxicological data.
SED can be compared with a relevant No Observed Adverse Effect Level (NOAEL) to calculate the Margin of Safety (MoS).
MoS = NOAEL ÷ SED
A higher MoS means that the estimated systemic exposure is further below the selected toxicological reference level. Whether the MoS is considered adequate depends on the substance, exposure scenario and applicable safety-assessment methodology.
No. A calculator is useful for estimating exposure and understanding the relationship between the key parameters, but a formal cosmetic safety assessment requires appropriate exposure assumptions, toxicological data, absorption information and professional assessment.
The concentration of an ingredient in a cosmetic product is not necessarily equal to the amount that reaches systemic circulation. Dermal absorption estimates how much of the exposed ingredient becomes systemically available and therefore directly affects the SED.
Yes. The same ingredient can have very different SED values depending on the cosmetic product, concentration, amount applied, frequency of use, absorption and body weight. SED is therefore always linked to a specific exposure scenario.

‍

Source: SCCS Notes of guidance for the testing of cosmetic ingredients and their safety evaluation

Contact

Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
Fill in the project questionnaire

This helps us to get to know you and your project better and to directly put together the right team for you. The questionnaire is especially helpful if you already have concrete ideas.

Start Now
Book a call

Have more questions?
Book a 30 minute free consultation with one of the founders.

Book a Call